The role of humoral and neuronal factors in the control of cerebral blood flow and metabolism is controversial. We studied the control of cerebral blood flow and metabolism under normal and stressful conditions. Our initial work was done with the hypercapnic and deoxyglucose models for stress, but the studies may be extended to other models of stress, e.g., hypoxia hypoglycemia and withdrawal from chronic alcohol consumption. Our initial observations demonstrated that the adrenal medualla was the source of factrs that controlled the response of cerebral blood flow to hypercapnic stress. Further work indicated that one of these factors was a delta-opioid peptide. Also, recent work demonstrated tht the response blood flow to hypercapnic stress is medicated through the EDRF (endothelium derived relaxing factor) system, and the sympathetic nervous system. Further details of the interaction of the delta-opiod system, the EDRF system, and the sympathetic nervous system in the activation of cerebral blood in hypercapnia are under investigation.